The spectrum of SCN1A-related infantile epileptic encephalopathies

Louise A. Harkin; Jacinta M. McMahon; Xenia Iona; Leanne Dibbens; James T. Pelekanos; Sameer M. Zuberi; Lynette G. Sadleir; Eva Andermann; Deepak Gill; Kevin Farrell; Mary Connolly; Thorsten Stanley; Michael Harbord; Frederick Andermann; Jing Wang; Sat Dev Batish; Jeffrey G. Jones; William K. Seltzer; Alison Gardner; Grant Sutherland; Samuel F. Berkovic; John C. Mulley; Ingrid E. Scheffer; Kim Abbott; Ian Andrews; Barry Appleton; Andrew Bleasel; Neil Buchanan; Christopher Burke; Anne Bye; Carol Camfield; Peter Camfield; Gabriel Chow; Kevin Collins; Mark Cook; J. Helen Cross; Yanick Crow; M. Daniela D'Agostino; Martin Delatycki; Colin Dunkley; Joe Fawke; Colin Ferrie; Michael Geraghty; Gail Graham; Padraic Grattan-Smith; Elizabeth Hallam; Lorie Hamiwka; Anton Harding; Simon Harvey; Michael Hayman; Ian Hufton; Peter Humphries; Pierre Jacob; Raimond Jacquemard; David Jamison; Philip Jardine; Steve Jones; Daniel Keene; Kent Kelley; David Ketteridge; Andrew Kim; Sara Kivity; Chris Kneebone; Andrew Kornberg; Chris Lamb; Cecilie Lander; Tally Lerman-Sagie; Dorit Lev; Richard Leventer; Mark Mackay; Steven Malone; Jim Manson; Ailsa McLellan; Philip Moore; Lakshmi Nagarajan; Margot Nash; Marina Nikanorova; Doug Nordli; Mary O'Regan; Robert Ouvrier; Jayesh Patel; Clair Pridmore; Venkat Ramesh; David Reutens; Peter Rowe; Lloyd Shield; Paul Shillito; Lindsay Smith; Claire Spooner; Geoffrey Wallace; Nathan Watemberg; William Whitehouse; Elaine Wirrell

doi:10.1093/brain/awm002

The spectrum of SCN1A-related infantile epileptic encephalopathies

Louise A. Harkin, Jacinta M. McMahon, Xenia Iona, Leanne Dibbens, James T. Pelekanos, Sameer M. Zuberi, Lynette G. Sadleir, Eva Andermann, Deepak Gill, Kevin Farrell, Mary Connolly, Thorsten Stanley, Michael Harbord, Frederick Andermann, Jing Wang, Sat Dev Batish, Jeffrey G. Jones, William K. Seltzer, Alison Gardner, Grant SutherlandSamuel F. Berkovic, John C. Mulley, Ingrid E. Scheffer^*, Kim Abbott, Ian Andrews, Barry Appleton, Andrew Bleasel, Neil Buchanan, Christopher Burke, Anne Bye, Carol Camfield, Peter Camfield, Gabriel Chow, Kevin Collins, Mark Cook, J. Helen Cross, Yanick Crow, M. Daniela D'Agostino, Martin Delatycki, Colin Dunkley, Joe Fawke, Colin Ferrie, Michael Geraghty, Gail Graham, Padraic Grattan-Smith, Elizabeth Hallam, Lorie Hamiwka, Anton Harding, Simon Harvey, Michael Hayman, Ian Hufton, Peter Humphries, Pierre Jacob, Raimond Jacquemard, David Jamison, Philip Jardine, Steve Jones, Daniel Keene, Kent Kelley, David Ketteridge, Andrew Kim, Sara Kivity, Chris Kneebone, Andrew Kornberg, Chris Lamb, Cecilie Lander, Tally Lerman-Sagie, Dorit Lev, Richard Leventer, Mark Mackay, Steven Malone, Jim Manson, Ailsa McLellan, Philip Moore, Lakshmi Nagarajan, Margot Nash, Marina Nikanorova, Doug Nordli, Mary O'Regan, Robert Ouvrier, Jayesh Patel, Clair Pridmore, Venkat Ramesh, David Reutens, Peter Rowe, Lloyd Shield, Paul Shillito, Lindsay Smith, Claire Spooner, Geoffrey Wallace, Nathan Watemberg, William Whitehouse, Elaine Wirrell

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

455 Scopus citations

Abstract

The relationship between severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) and the related syndrome SMEI-borderland (SMEB) with mutations in the sodium channel alpha 1 subunit gene SCN1A is well established. To explore the phenotypic variability associated with SCN1A mutations, 188 patients with a range of epileptic encephalopathies were examined for SCN1A sequence variations by denaturing high performance liquid chromatography and sequencing. All patients had seizure onset within the first 2 years of life. A higher proportion of mutations were identified in patients with SMEI (52/66; 79%) compared to patients with SMEB (25/36; 69%). By studying a broader spectrum of infantile epileptic encephalopathies, we identified mutations in other syndromes including cryptogenic generalized epilepsy (24%) and cryptogenic focal epilepsy (22%). Within the latter group, a distinctive subgroup designated as severe infantile multifocal epilepsy had SCN1A mutations in three of five cases. This phenotype is characterized by early onset multifocal seizures and later cognitive decline. Knowledge of an expanded spectrum of epileptic encephalopathies associated with SCN1A mutations allows earlier diagnostic confirmation for children with these devastating disorders.

Original language	English
Pages (from-to)	843-852
Number of pages	10
Journal	Brain
Volume	130
Issue number	3
DOIs	https://doi.org/10.1093/brain/awm002
State	Published - Mar 2007

Funding

Funders	Funder number
National Health and Medical Research Council of Australia
Thyne-Reid Charitable Trusts and Bionomics Ltd

Keywords

Channelopathies
Epileptic encephalopathy
SCN1A
SMEB
SMEI

Access to Document

10.1093/brain/awm002

Cite this

Harkin, L. A., McMahon, J. M., Iona, X., Dibbens, L., Pelekanos, J. T., Zuberi, S. M., Sadleir, L. G., Andermann, E., Gill, D., Farrell, K., Connolly, M., Stanley, T., Harbord, M., Andermann, F., Wang, J., Batish, S. D., Jones, J. G., Seltzer, W. K., Gardner, A., ... Wirrell, E. (2007). The spectrum of SCN1A-related infantile epileptic encephalopathies. Brain, 130(3), 843-852. https://doi.org/10.1093/brain/awm002

@article{2eb029b90db5409fa2f90a36d5133a66,

title = "The spectrum of SCN1A-related infantile epileptic encephalopathies",

abstract = "The relationship between severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) and the related syndrome SMEI-borderland (SMEB) with mutations in the sodium channel alpha 1 subunit gene SCN1A is well established. To explore the phenotypic variability associated with SCN1A mutations, 188 patients with a range of epileptic encephalopathies were examined for SCN1A sequence variations by denaturing high performance liquid chromatography and sequencing. All patients had seizure onset within the first 2 years of life. A higher proportion of mutations were identified in patients with SMEI (52/66; 79%) compared to patients with SMEB (25/36; 69%). By studying a broader spectrum of infantile epileptic encephalopathies, we identified mutations in other syndromes including cryptogenic generalized epilepsy (24%) and cryptogenic focal epilepsy (22%). Within the latter group, a distinctive subgroup designated as severe infantile multifocal epilepsy had SCN1A mutations in three of five cases. This phenotype is characterized by early onset multifocal seizures and later cognitive decline. Knowledge of an expanded spectrum of epileptic encephalopathies associated with SCN1A mutations allows earlier diagnostic confirmation for children with these devastating disorders.",

keywords = "Channelopathies, Epileptic encephalopathy, SCN1A, SMEB, SMEI",

author = "Harkin, {Louise A.} and McMahon, {Jacinta M.} and Xenia Iona and Leanne Dibbens and Pelekanos, {James T.} and Zuberi, {Sameer M.} and Sadleir, {Lynette G.} and Eva Andermann and Deepak Gill and Kevin Farrell and Mary Connolly and Thorsten Stanley and Michael Harbord and Frederick Andermann and Jing Wang and Batish, {Sat Dev} and Jones, {Jeffrey G.} and Seltzer, {William K.} and Alison Gardner and Grant Sutherland and Berkovic, {Samuel F.} and Mulley, {John C.} and Scheffer, {Ingrid E.} and Kim Abbott and Ian Andrews and Barry Appleton and Andrew Bleasel and Neil Buchanan and Christopher Burke and Anne Bye and Carol Camfield and Peter Camfield and Gabriel Chow and Kevin Collins and Mark Cook and Cross, {J. Helen} and Yanick Crow and D'Agostino, {M. Daniela} and Martin Delatycki and Colin Dunkley and Joe Fawke and Colin Ferrie and Michael Geraghty and Gail Graham and Padraic Grattan-Smith and Elizabeth Hallam and Lorie Hamiwka and Anton Harding and Simon Harvey and Michael Hayman and Ian Hufton and Peter Humphries and Pierre Jacob and Raimond Jacquemard and David Jamison and Philip Jardine and Steve Jones and Daniel Keene and Kent Kelley and David Ketteridge and Andrew Kim and Sara Kivity and Chris Kneebone and Andrew Kornberg and Chris Lamb and Cecilie Lander and Tally Lerman-Sagie and Dorit Lev and Richard Leventer and Mark Mackay and Steven Malone and Jim Manson and Ailsa McLellan and Philip Moore and Lakshmi Nagarajan and Margot Nash and Marina Nikanorova and Doug Nordli and Mary O'Regan and Robert Ouvrier and Jayesh Patel and Clair Pridmore and Venkat Ramesh and David Reutens and Peter Rowe and Lloyd Shield and Paul Shillito and Lindsay Smith and Claire Spooner and Geoffrey Wallace and Nathan Watemberg and William Whitehouse and Elaine Wirrell",

note = "Funding Information: We thank the patients and their families for participating in this research. Funding was provided by the National Health and Medical Research Council of Australia, Thyne-Reid Charitable Trusts and Bionomics Ltd.",

year = "2007",

month = mar,

doi = "10.1093/brain/awm002",

language = "אנגלית",

volume = "130",

pages = "843--852",

journal = "Brain",

issn = "0006-8950",

publisher = "Oxford University Press",

number = "3",

}

Harkin, LA, McMahon, JM, Iona, X, Dibbens, L, Pelekanos, JT, Zuberi, SM, Sadleir, LG, Andermann, E, Gill, D, Farrell, K, Connolly, M, Stanley, T, Harbord, M, Andermann, F, Wang, J, Batish, SD, Jones, JG, Seltzer, WK, Gardner, A, Sutherland, G, Berkovic, SF, Mulley, JC, Scheffer, IE, Abbott, K, Andrews, I, Appleton, B, Bleasel, A, Buchanan, N, Burke, C, Bye, A, Camfield, C, Camfield, P, Chow, G, Collins, K, Cook, M, Cross, JH, Crow, Y, D'Agostino, MD, Delatycki, M, Dunkley, C, Fawke, J, Ferrie, C, Geraghty, M, Graham, G, Grattan-Smith, P, Hallam, E, Hamiwka, L, Harding, A, Harvey, S, Hayman, M, Hufton, I, Humphries, P, Jacob, P, Jacquemard, R, Jamison, D, Jardine, P, Jones, S, Keene, D, Kelley, K, Ketteridge, D, Kim, A, Kivity, S, Kneebone, C, Kornberg, A, Lamb, C, Lander, C, Lerman-Sagie, T , Lev, D, Leventer, R, Mackay, M, Malone, S, Manson, J, McLellan, A, Moore, P, Nagarajan, L, Nash, M, Nikanorova, M, Nordli, D, O'Regan, M, Ouvrier, R, Patel, J, Pridmore, C, Ramesh, V, Reutens, D, Rowe, P, Shield, L, Shillito, P, Smith, L, Spooner, C, Wallace, G, Watemberg, N, Whitehouse, W & Wirrell, E 2007, 'The spectrum of SCN1A-related infantile epileptic encephalopathies', Brain, vol. 130, no. 3, pp. 843-852. https://doi.org/10.1093/brain/awm002

TY - JOUR

T1 - The spectrum of SCN1A-related infantile epileptic encephalopathies

AU - Harkin, Louise A.

AU - McMahon, Jacinta M.

AU - Iona, Xenia

AU - Dibbens, Leanne

AU - Pelekanos, James T.

AU - Zuberi, Sameer M.

AU - Sadleir, Lynette G.

AU - Andermann, Eva

AU - Gill, Deepak

AU - Farrell, Kevin

AU - Connolly, Mary

AU - Stanley, Thorsten

AU - Harbord, Michael

AU - Andermann, Frederick

AU - Wang, Jing

AU - Batish, Sat Dev

AU - Jones, Jeffrey G.

AU - Seltzer, William K.

AU - Gardner, Alison

AU - Sutherland, Grant

AU - Berkovic, Samuel F.

AU - Mulley, John C.

AU - Scheffer, Ingrid E.

AU - Abbott, Kim

AU - Andrews, Ian

AU - Appleton, Barry

AU - Bleasel, Andrew

AU - Buchanan, Neil

AU - Burke, Christopher

AU - Bye, Anne

AU - Camfield, Carol

AU - Camfield, Peter

AU - Chow, Gabriel

AU - Collins, Kevin

AU - Cook, Mark

AU - Cross, J. Helen

AU - Crow, Yanick

AU - D'Agostino, M. Daniela

AU - Delatycki, Martin

AU - Dunkley, Colin

AU - Fawke, Joe

AU - Ferrie, Colin

AU - Geraghty, Michael

AU - Graham, Gail

AU - Grattan-Smith, Padraic

AU - Hallam, Elizabeth

AU - Hamiwka, Lorie

AU - Harding, Anton

AU - Harvey, Simon

AU - Hayman, Michael

AU - Hufton, Ian

AU - Humphries, Peter

AU - Jacob, Pierre

AU - Jacquemard, Raimond

AU - Jamison, David

AU - Jardine, Philip

AU - Jones, Steve

AU - Keene, Daniel

AU - Kelley, Kent

AU - Ketteridge, David

AU - Kim, Andrew

AU - Kivity, Sara

AU - Kneebone, Chris

AU - Kornberg, Andrew

AU - Lamb, Chris

AU - Lander, Cecilie

AU - Lerman-Sagie, Tally

AU - Lev, Dorit

AU - Leventer, Richard

AU - Mackay, Mark

AU - Malone, Steven

AU - Manson, Jim

AU - McLellan, Ailsa

AU - Moore, Philip

AU - Nagarajan, Lakshmi

AU - Nash, Margot

AU - Nikanorova, Marina

AU - Nordli, Doug

AU - O'Regan, Mary

AU - Ouvrier, Robert

AU - Patel, Jayesh

AU - Pridmore, Clair

AU - Ramesh, Venkat

AU - Reutens, David

AU - Rowe, Peter

AU - Shield, Lloyd

AU - Shillito, Paul

AU - Smith, Lindsay

AU - Spooner, Claire

AU - Wallace, Geoffrey

AU - Watemberg, Nathan

AU - Whitehouse, William

AU - Wirrell, Elaine

N1 - Funding Information: We thank the patients and their families for participating in this research. Funding was provided by the National Health and Medical Research Council of Australia, Thyne-Reid Charitable Trusts and Bionomics Ltd.

PY - 2007/3

Y1 - 2007/3

N2 - The relationship between severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) and the related syndrome SMEI-borderland (SMEB) with mutations in the sodium channel alpha 1 subunit gene SCN1A is well established. To explore the phenotypic variability associated with SCN1A mutations, 188 patients with a range of epileptic encephalopathies were examined for SCN1A sequence variations by denaturing high performance liquid chromatography and sequencing. All patients had seizure onset within the first 2 years of life. A higher proportion of mutations were identified in patients with SMEI (52/66; 79%) compared to patients with SMEB (25/36; 69%). By studying a broader spectrum of infantile epileptic encephalopathies, we identified mutations in other syndromes including cryptogenic generalized epilepsy (24%) and cryptogenic focal epilepsy (22%). Within the latter group, a distinctive subgroup designated as severe infantile multifocal epilepsy had SCN1A mutations in three of five cases. This phenotype is characterized by early onset multifocal seizures and later cognitive decline. Knowledge of an expanded spectrum of epileptic encephalopathies associated with SCN1A mutations allows earlier diagnostic confirmation for children with these devastating disorders.

AB - The relationship between severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) and the related syndrome SMEI-borderland (SMEB) with mutations in the sodium channel alpha 1 subunit gene SCN1A is well established. To explore the phenotypic variability associated with SCN1A mutations, 188 patients with a range of epileptic encephalopathies were examined for SCN1A sequence variations by denaturing high performance liquid chromatography and sequencing. All patients had seizure onset within the first 2 years of life. A higher proportion of mutations were identified in patients with SMEI (52/66; 79%) compared to patients with SMEB (25/36; 69%). By studying a broader spectrum of infantile epileptic encephalopathies, we identified mutations in other syndromes including cryptogenic generalized epilepsy (24%) and cryptogenic focal epilepsy (22%). Within the latter group, a distinctive subgroup designated as severe infantile multifocal epilepsy had SCN1A mutations in three of five cases. This phenotype is characterized by early onset multifocal seizures and later cognitive decline. Knowledge of an expanded spectrum of epileptic encephalopathies associated with SCN1A mutations allows earlier diagnostic confirmation for children with these devastating disorders.

KW - Channelopathies

KW - Epileptic encephalopathy

KW - SCN1A

KW - SMEB

KW - SMEI

UR - http://www.scopus.com/inward/record.url?scp=33947123754&partnerID=8YFLogxK

U2 - 10.1093/brain/awm002

DO - 10.1093/brain/awm002

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 17347258

AN - SCOPUS:33947123754

SN - 0006-8950

VL - 130

SP - 843

EP - 852

JO - Brain

JF - Brain

IS - 3

ER -

The spectrum of SCN1A-related infantile epileptic encephalopathies

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